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Altered Urine Metabolome in Patients with Bladder Cancer - Expert Commentary

Risk factors associated with bladder cancer, such as smoking, age, and BMI, can alter metabolic profiles and can be evaluated in patients through metabolomic analysis. Recently, Jacyna et al. collected urine from ten patients (eight men and two women) with non-muscle-invasive bladder cancer at three different time points: before trans-urethral resection of bladder tumor (TURBT), the day after TURBT, and at a follow-up visit two weeks later. These samples were analyzed using high-performance liquid chromatography time-of-flight mass spectrometry (HPLC-TOF/MS) and gas chromatography with triple quadrupole mass spectrometry (GCQqQ/MS).

This work builds on a previously published study in which the same group identified metabolites that differentiate between bladder cancer patients and controls. In the current study, the researchers analyzed the levels of these metabolites first to determine changes across the time points. Propanoic acid, 2-deoxy-ribonic acid, and benzenediol increased the day after TURBT significantly and returned to baseline levels at the two-week time point. The concentration of meso-erythritol decreased between the first and second time points and then reached baseline again by the third time point. S-adenosylmethionine was only detectable at the second timepoint.

When comparing urine from patients with bladder cancer to healthy controls, the most significant differences in concentration were observed for Hippuric acid, pentanedioic acid, and uridine metabolites. Most of the altered metabolites play a role in amino acid metabolism. The authors hypothesize that this is due to tumor growth, cell proliferation, and increased cellular activity. They posit that elevated levels of methylguanine could be due to increased nucleic acid turnover or increases in methylation, which are known features of many cancers.

Limitations of this exploratory study include the small sample size. In addition, several clinical factors such as BMI that can affect metabolism are potential confounders for the observed differences. Additional studies are needed to validate the results. If validated in more extensive studies, these results open new avenues for metabolomic biomarkers of bladder cancer.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York 

References: 

  1. Jacyna, J., Kordalewska, M., Artymowicz, M., Markuszewski, M., Matuszewski, M., & Markuszewski, M. J. (2022). Pre- and Post-Resection Urine Metabolic Profiles of Bladder Cancer Patients: Results of Preliminary Studies on Time Series Metabolomics Analysis. Cancers, 14(5), 1210. https://doi.org/10.3390/cancers14051210
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